FGF5 protects heart from sepsis injury by attenuating cardiomyocyte pyroptosis through inhibiting CaMKII/NFκB signaling.

Sepsis accompanied by myocardial injury is an important cause of multiple organ dysfunction, and its underlying molecular mechanism is not fully clear. Although diverse effects of fibroblast growth factor (FGF) in heart have been discovered till now, the specific role of FGF5 in heart remains unclear. Therefore, our study aims to explore the possible impacts of FGF5 on sepsis-induced cardiac injury. Sepsis-induced cardiac injury was established through administration of lipopolysaccharide (LPS). The expression level of FGF5 in sepsis heart was decreased, and injection of FGF5-overexpressing adenovirus attenuated cardiac injury reflected by echocardiographic and pathological findings. Besides, FGF5 overexpression, not only in vivo heart but also in vitro cardiomyocytes, reduced the levels of oxidative stress and pyroptosis resulted from LPS. In addition, overexpression of FGF5 reduced LPS-activated the levels of phosphorylated CaMKII (p-CaMKII), p-NFκB, NLRP3, caspase-1, IL-1β and IL-18. Furthermore, KN93, the inhibitor of CaMKII, exerted the similarly protective effects on LPS-induced pyroptosis. In summary, our study implied the beneficial effects of FGF5 on LPS-induced cardiac injury, which was at least partially attributed to the inhibition of CaMKII-mediated pyroptotic signaling.